The 5-pyrrolyl-2-pyridylmethylsulfinylbenzimidazole derivative of formula (1), as defined above, is a novel compound developed by the present inventors, and applications for approval as a product patent are presently pending or granted in 17 countries including Korea, Japan, the United States, etc. It acts as a proton pump inhibitor like the widely known omeprazole, lansoprazole, etc., but is very unstable under acidic or neutral conditions, which may cause several problems in formulation processes.
The 5-pyrrolyl-2-pyridylmethylsulfinylbenzimidazole derivative (in the present specification, it is referred to as `the active ingredient of the present invention`) is very stable under alkali conditions of pH 7.6 or more, and yet it has a half time of 40 minutes or less under acidic conditions (about pH 4.0) and has a half time of 35 hours at neutral conditions (pH 7.0). Therefore, it has been recognized as more unstable under acidic or neutral conditions than omeprazole or lansoprazole which is also unstable under the same condition. Such unstability may cause many problems during storage or distribution. Particularly, it is desired to adjust the ambient circumstance to a low temperature of 4.degree. C. or less, anhydrous and alkaline condition since the degradation of the active ingredient of the present invention is highly facilitated by the moisture and acidic conditions when the storage or distribution temperature becomes 40.degree. C. or more.
The general way for stabilizing the acid-unstable substances is to make an alkaline environment as well as to intercept the influx of moisture from the ambient. But, the present inventors have found that the desired stabilizing effect can hardly be obtained by simply mixing the acid-unstable active ingredient of the present invention with an alkali compound.
Thus, the present inventors have extensively studied to establish a method through which the active ingredient of the present invention can be stablized in a form of microgranule. As a result, we found that such a microgranule can be prepared by combining an alkali compound with the active ingredient of the present invention in a specific mole ratio to adjust the acidity and simultaneously by using a water-soluble polymer as a binding agent in a specific content, and then completed the present invention. Particularly, we have noticed as a result of intensive researches that a certain alkaline salt, that is magnesium hydroxide, among the known alkali compounds, is highly appropriate for stabilizing the active ingredient of the present invention.